Project Summary/Abstract The study of catalysis to improve synthetic methodologies and enable the synthesis of biologically active molecules is an essential component of modern medicine. Minimal oligopeptide catalysts are a promising type of catalyst as they occupy a middle ground between enzymes and small molecule organocatalysts, containing some of the complexity of proteins with enhanced synthetic accessibility and robustness. Although minimal peptides lack the intricate three-dimensional environment of a full size folded protein, researchers have found that including natural and unnatural turn-nucleating residues can induce secondary structure conformations that are conducive to catalysis. Even for short sequences, it remains difficult to rationally design catalytic sequences, so it would be useful to study catalytic peptides using parallel or combinatorial libraries. However, the evaluation of catalytic activity using conventional techniques is often a limitation to studying these large sequence spaces. Herein, we propose to use competitive dye displacement as a means to detect the formation of product in crude reaction mixtures, thus enabling visible light spectroscopy to be used as a rapid means of evaluating the activity of peptide catalysts. This assay will be developed for aldol reactions, and we will use the assay to explore the role of turn-nucleating residues in a previously reported minimal peptide aldol catalyst. The rapid nature of the absorbance-based assay will allow the study of catalytic properties of larger libraries than would otherwise be feasible with conventional methods, and in the future this dye displacement assay can be used to study and optimize other types of aldol catalysts as well.